Cancer is a disease characterized by uncontrolled cellular division and growth. Cancer cells gain the capacity to invade the organ of origin, spread through the bloodstream and lymph to distal organs and establish and growth on them. That is a highly heterogeneous process, but common for over 200 types of cancers of quite varied evolution. Several genes have to be simultaneously altered for developing the disease. All these properties increase the complexity for studying and unraveling the mechanisms of malignancies, and therefore, cancer research is a wide and multidisciplinary field and involves several lines of investigation. Significantly, this disease is the second death cause in relevance worldwide and is expected to become the first one for the year 2020, even more deadly than cardiovascular diseases (Forteza F (2004) Avances médicos de Cuba. 40:33).
In fact, cancer is already the first death cause in developed countries and the second death cause in the developing ones (World Health Organization. The Global Burden of Disease: 2004 Update. Geneva: World Health Organization; 2008). Its incidence is rising in these last due to increased aging population, and even more frequently because of cancer-prone lifestyles—physical inactivity, smoking and “western” diets.
There were estimates at GLOBOCAN 2008 of 12.7 millions of patients living with cancer and 7.6 million deaths in 2008; of them, 56% of patients and 64% of deaths occurred in developing countries (Ferlay J, Shin H R, Bray F, Forman D, Mathers C D, Parkin D. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10. Lyon, France: International Agency for Research on Cancer; Available from: http://globocan.iarc.fr. 2010. Accessed Aug. 17, 2010).
Cancer survival tends to be far lower in developing countries, probably because of combined late diagnosis and the limited access to timely and appropriate treatment and regardless of the cytotoxic drugs already available and being optimized for cancer treatment. New biological molecules are required to create a new generation of anticancer medicines, more efficacious and safer in a near future and able to significantly permeate the market of cancer therapeutics.
Currently, it has been widely accepted that to be effective, cancer treatment have to combine different action principles, such as: direct action on tumor cells and effect on the tumor environment. This can be achieved by combining molecules separately bearing each of these properties, or simultaneously showing both of them. Undoubtedly, this last type of molecules is advantageous since the pharmacological and economical points of view. Preclinical trials with angiogenesis inhibitors intended to interrupt oxygen and nutrient supply to the tumor have shown very promising results, frequently achieving complete or partial tumor regression in the absence of resistance against the inhibitor. Up to now, the major achievement in clinical trials has been the sustained compensation of the disease for a given period of time. For that purpose, anti-angiogenic agents are being used as adjuvant therapy for other antitumorals in combination.
Results from clinical trials have shown that single targeting of angiogenesis modulators is insufficient for a sustained inhibitory response. There is an increasing demand for more effective anti-angiogenic agents able to arrest and also revert tumor growth, in order to achieve a significant increase in patient's lifespan and quality of life when compared to treatments established.
Currently available peptides represent a small fraction among the myriad of agents being used for therapeutic purposes. In fact, the potential of peptides is being improved with the aid of new technologies for modifying their structure, pharmacokinetics, biodistribution, stability and preclinical applications. Particularly, they have gained relevance in cancer therapy because of the novel methodologies available for modifying them and increasing their anticancer efficacy (Li, Zhi J.; Cho, Chi H. Current Pharmaceutical Design, 16 (10), April 2010, pp. 1180-1189).
Several studies have shown the affordability of using peptides for cancer diagnosis and therapy. Some of them are in advanced clinical phases of development, and other new generations have being appearing in the last years, with promising preclinical results.
The cytotoxic activity of a lytic peptide designed to bind the epidermal growth factor receptor was demonstrated in several human cancer cell lines. It was evidenced that conformational changes arising from binding of the lytic peptide increased its selectivity for association to the membrane of cancer cells, and this acquired synergic action resulted in a selective destruction of the tumor cells. Treatment with the lytic peptide binding the epidermal growth factor receptor exhibited cytotoxic activity in vitro against cancer cells resistant to tyrosine kinase inhibitors with K-ras mutations (Kohno, Masayuki. European Journal of Cancer 47(5), p. 773, March 2011).
Cell penetrating peptides are commonly coupled to oligonucleotides to increase their effectiveness in cancer therapy. For this purpose, cell penetrating peptides have being designed comprising a glutamate peptide linked to the N-terminus of the Oct6 NLS, which demonstrated to co-localize into the cell nucleus, and also its uptake by pancreatic and prostate cancer cell lines (Lewis, H Dan. BMC Biotechnology, 10(1), p. 79, October 2010).
A peptide fragment from the tissue factor pathway inhibitor (TFPI), which is a naturally anticoagulating protein, was able to block tumor growth and angiogenesis in in vivo models. Moreover, it inhibited tumor metastasis and the growth of new blood vessels with no apparent effect on the normal ones (HEMBROUGH Todd A.; RUIZ Jose F.; SWERDLOW Bonnie M.; SWARTZ Glenn M.; HAMMERS Hans J.; ZHANG Li; PLUM Stacy M.; WILLIAMS Mark S.; STRICKLAND Dudley K.; PRIBLUDA Victor S. Blood A. 2004, vol. 103, n° 9, pp. 3374-3380).
The development of more selective agents for imaging and treatment of different tumors is the current tendency in cancer therapy and diagnosis. In this sense, peptides are small amino acid sequences which can be obtained or designed to bind a predetermined molecular target, and they are potentially able to interfere with its function. These specific peptides can inhibit components of specific signals essential for cancer development and progression.
Serralysin is the major extracellular protein of the bacterium Serratia marcescens CMIB4202 and is associated to the pathogenicity of this microorganism in humans, with attributed antitumoral properties dependent on its catalytic activity (Wu Jun, Akaike T, Hayashida K, et al., (2001) Japanese J. Cancer Res. 92:439-451). In this strain (S. marcescens CMIB4202), the most abundant extracellular protein is the p50 protein, which belongs to the family of Serralysins (SERMA). It is known that the polypeptide comprising the C-terminal non-catalytitc domain of this serralysin (denominated p25) is a potent inhibitor of endothelial proliferation and growth of primary tumors and metastasis in vivo (Abrahantes-Pérez M C et al., “Pharmaceutical composition containing polypeptide fragments of serralysins”. International Patent Application No. WO 2006/005268). This polypeptide was named CIGB370r when expressed recombinant in Escherichia coli. 
There is a great demand on identifying and obtaining more potent antitumoral agents because of the increasing incidence of this disease, to replace or complement current cancer therapy in those patients requiring it, in spite of multiple drugs available for that purpose.